Reduced and delayed untwisting of the left ventricle in patients with hypertension and left ventricular hypertrophy: a study using two-dimensional speckle tracking imaging.

AIMS: Newly developed two-dimensional ultrasound speckle tracking imaging allows measurements of left ventricular (LV) rotation and twist. Because LV untwisting predominantly occurs during the isovolumic relaxation period, its assessment reflects the process of LV relaxation. The aim of this study was to examine whether LV hypertrophy (LVH) adversely affects LV untwisting and abnormalities in LV untwisting could become a novel marker in assessing LV relaxation abnormalities. METHODS AND RESULTS: We acquired basal and apical LV short-axis images in 49 hypertensive patients. Using two-dimensional strain software, a time-domain speckle tracking was performed, and the mean value of LV rotation was obtained at each plane. LV twist was defined as apical rotation relative to the base. In order to adjust for inter-subject differences in heart rate, the time sequence was normalized to the percentage of systolic and diastolic duration. The degree of LV untwisting was calculated as the percentage of systolic twist : untwisting = (TwistES-Twistt/TwistES) x 100, where Twistt is twist at time t and TwistES is twist at end-systole. Although peak systolic twist was not different, early diastolic LV untwisting and untwisting rate during isovolumic relaxation period was significantly delayed and reduced in parallel to the severity of LVH, as assessed by LV mass index. CONCLUSION: The observed delayed and reduced diastolic untwisting during the isovolumic relaxation period noted in hypertensive patients with LVH may contribute towards the LV relaxation abnormality. Two-dimensional speckle tracking imaging is a novel tool which can be used for the non-invasive assessment of LV relaxation.     

Illusory contours activate specific regions in human visual cortex: evidence from functional magnetic resonance imaging.

The neural basis for perceptual grouping operations in the human visual system, including the processes which generate illusory contours, is fundamental to understanding human vision. We have employed functional magnetic resonance imaging to investigate these processes noninvasively. Images were acquired on a GE Signa 1.5T scanner equipped for echo planar imaging with an in-plane resolution of 1.5 x 1.5 mm and slice thicknesses of 3.0 or 5.0 mm. Visual stimuli included nonaligned inducers (pacmen) that created no perceptual contours, similar inducers at the corners of a Kanizsa square that created illusory contours, and a real square formed by continuous contours. Multiple contiguous axial slices were acquired during baseline, visual stimulation, and poststimulation periods. Activated regions were identified by a multistage statistical analysis of the activation for each volume element sampled and were compared across conditions. Specific brain regions were activated in extrastriate cortex when the illusory contours were perceived but not during conditions when the illusory contours were absent. These unique regions were found primarily in the right hemisphere for all four subjects and demonstrate that specific brain regions are activated during the kind of perceptual grouping operations involved in illusory contour perception.     

Quality improvement in the door‐to‐balloon times for ST‐elevation myocardial infarction patients presenting without chest pain

Objective: To assess a quality improvement initiative aimed at minimizing door‐to‐balloon (DTB) times for ST‐elevation myocardial infarction (STEMI) patients presenting without chest pain. Background: Timely percutaneous coronary intervention (PCI) is the cornerstone of STEMI care. The absence of chest pain delays PCI. Improvements in DTB times may need to focus on atypical presentation patients. Methods: We compared DTB times on all STEMI patients admitted through the emergency department who underwent PCI before (Phase I; October 2004–June 2007) and after (Phase II; July 2007–October 2009) the quality improvement effort, which mandated rapid electrocardiogram (ECG) triage for an expanded list of presenting symptoms. Results: In Phase I (69 patient, 60 with chest pain), patients with chest pain had a shorter mean time to first ECG (ECG Interval) by 32.0 min (P < 0.01) and nonsignificantly faster mean DTB time by 42.0 min (P = 0.07) compared to patients who presented without chest pain. In Phase II (62 patients, 56 with chest pain) compared to Phase I, mean ECG interval decreased by 44 min (P = 0.02) and mean DTB time by 99 min (P = 0.01) in patients without chest pain, eliminating the differences in ECG intervals between typical and atypical presentations (12 min vs. 11 min, P = 0.91). Multivariable analysis controlling for on/off hours and patient characteristics confirmed these findings. Conclusions: A simple modification of emergency room ECG triage protocol, which expands indications for rapid ECG performance, was successful in improving rapid reperfusion for patients with STEMI presenting without chest pain. © 2011 Wiley‐Liss, Inc.     

Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis

The protective antigen (PA) moiety of anthrax toxin transports edema factor and lethal factor to the cytosol of mammalian cells by a mechanism that depends on its ability to oligomerize and form pores in the endosomal membrane. Previously, some mutated forms of PA, designated dominant negative (DN), were found to coassemble with wild-type PA and generate defective heptameric pore-precursors (prepores). Prepores containing DN-PA are impaired in pore formation and in translocating edema factor and lethal factor across the endosomal membrane. To create a more comprehensive map of sites within PA where a single amino acid replacement can give a DN phenotype, we used automated systems to generate a Cys-replacement mutation for each of the 568 residues of PA63, the active 63-kDa proteolytic fragment of PA. Thirty-three mutations that reduced PA's ability to mediate toxicity at least 100-fold were identified in all four domains of PA63. A majority (22) were in domain 2, the pore-forming domain. Seven of the domain-2 mutations, located in or adjacent to the 2beta6 strand, the 2beta7 strand, and the 2beta10-2beta11 loop, gave the DN phenotype. This study demonstrates the feasibility of high-throughput scanning mutagenesis of a moderate sized protein. The results show that DN mutations cluster in a single domain and implicate 2beta6 and 2beta7 strands and the 2beta10-2beta11 loop in the conformational rearrangement of the prepore to the pore. They also add to the repertoire of mutations available for structure-function studies and for designing new antitoxic agents for treatment of anthrax.